Association of overweight/obesity and overweight/obesity-related metabolic dysfunction-associated steatotic liver disease in young adults with coronary artery calcification later in life.

AIM: The association of overweight/obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) in young adulthood with subclinical atherosclerosis [coronary artery calcification (CAC) and abdominal aortic calcification (AAC)] by middle age is unknown. METHOD: In total, 2274 participants aged 28-39 years from the coronary artery risk development in young adults study at year 10 (1995-1996) who were re-examined 15 years later were included. CAC and AAC were measured at year 25 using computed tomography. We examined the utility of three young adult phenotypes (lean group; overweight/obese group; overweight/obese MASLD group) at year 10 in predicting CAC or AAC by middle age. Modified Poisson regression was used to estimate the association between groups and CAC, and AAC. Independent determinates of CAC and AAC were determined with linear regression models. RESULTS: Compared with individuals categorized as lean in young adulthood, the relative risk for CAC by middle age was 1.09 (95% confidence interval: 0.93-1.28) for those with overweight/obesity and 1.32 (95% confidence interval: 1.08-1.61) for those with overweight/obesity-related MASLD. For AAC, no difference was observed between these three groups. Group, systolic blood pressure and group × systolic blood pressure interaction were all the independent determinates for CAC. CONCLUSION: In this study, young adults with overweight/obesity-related MASLD have a higher risk of developing CAC by middle age. These abnormalities are only partially explained by traditional cardiovascular risk factors, and overweight/obesity-related MASLD has an independent impact on CAC. Our study provides evidence for identifying young adults at higher risk of developing subclinical atherosclerosis.

Design, synthesis and biological evaluation of 6-chloro-quinolin-2-one derivatives as novel FXIa inhibitors.

A series of 6-chloro-quinolin-2-one derivatives were designed and synthesized as FXIa inhibitors by exploration of P1, P1 prime and P2 prime groups. Each compound was accessed for inhibitory effect on FXIa and some of them were evaluated in the clotting assay. 14c demonstrated excellent in-vitro potency (FXIa IC50: 15 nM, 2 x aPTT: 6.8 µM) and good in-vivo efficacy (prolonged in-vivo aPTT by more than 1-fold but not PT). Moreover, the pharmacokinetics property of 14c were evaluated following intravenous administration in rats, which indicated that 14c probably will be a clinical candidate for intravenous administration.

Partially PEG-Grafted Poly(Terphenyl Piperidinium) Anion Exchange Membranes with Balanced Properties for Alkaline Fuel Cells.

Poly(ethylene glycol) (PEG) or oligo (ethylene glycol) (OEG) grafted anion exchange membranes (AEMs) exhibit improved ionic conductivity, high alkaline stability, and subsequent boosted AEM fuel cell performance, but too much PEG/OEG side chains may can result in a reduction in the ion exchange capacity (IEC), which can have adverse effects on ion transport. Here, a series of partially PEG-grafted poly(terphenyl piperidinium) with different side chain length were synthesized using simple post-polymerization modification to produce AEMs with balanced properties. The polar and flexible PEG side chains were responsible for the controlled water uptake and swelling, superior hydroxide conductivity (122 mS cm-1 at 80 °C with a IEC of 1.99 mmol g-1), and enhanced alkaline stability compared to the reference sample without PEG grafts (PTP). More importantly, the performance of AEM fuel cell (AEMFC) with the membrane containing partial PEG side chains surpassed that with PTP membrane, demonstrating a highest peak power density of 1110 mW cm-2 at 80 °C under optimized conditions. This work provided a novel approach to the fabrication of high-performance AEM materials with balanced properties for alkaline fuel cell application. This article is protected by copyright. All rights reserved.

Efficacy and Safety of Avapritinib in Treating Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Phase I/II, Open-Label, Multicenter Study.

BACKGROUND: Avapritinib is a type 1 kinase inhibitor designed to potently and selectively inhibit oncogenic KIT/PDGFRA mutants by targeting the kinase active conformation. This multicenter, single-arm, open-label, phase I/II bridging study of NAVIGATOR in Chinese patients evaluated the safety and the antineoplastic activity of avapritinib in Chinese patients with unresectable/metastatic gastrointestinal stromal tumors (GIST). METHODS: Phase I comprised dose escalation for safety and phase II dose determination. Phase II comprised dose expansion for safety/efficacy evaluations in patients with PDGFRA D842V mutations or patients having received at least 3 lines of therapy without PDGFRA D842V mutations. The primary endpoints were recommended phase II dose, safety, and Independent Radiology Review Committee (IRRC)-assessed objective response rate (ORR). RESULTS: No dose-limiting toxicities occurred (n = 10); the recommended phase II dose was avapritinib 300 mg once daily orally. Fifty-nine patients initially received avapritinib 300 mg. Common grade ≥3 treatment-related adverse events were anemia, decreased white blood cell count, increased blood bilirubin levels, and decreased neutrophil count. In patients with PDGFRA D842V mutations, IRRC- and investigator-assessed ORRs were 75% and 79%, respectively; clinical benefit rates were both 86%. Median duration of response/progression-free survival were not reached. IRCC- and investigator-assessed ORRs in patients in the fourth- or later-line setting were 22% and 35%, respectively. Median progression-free survivals were 5.6 months for both. Overall survival data were immature and not calculated. CONCLUSION: Avapritinib was generally well tolerated and showed marked anti-tumor activity in Chinese patients with GIST bearing PDGFRA D842V mutations and notable efficacy as fourth- or later-line monotherapy (ClinicalTrials.gov Identifier: NCT04254939).

Leptin-deficient ob/ob mice exhibit periodontitis phenotype and altered oral microbiome.

BACKGROUND AND OBJECTIVE: Leptin-deficient obesity is associated with various systemic diseases including diabetes and low bone mass phenotype. However, the periodontal status of leptin-deficient obese individuals is still unclear. In this study, we aimed to analyze the periodontal status, alveolar bone phenotype, and oral microbiome status in leptin-deficient obese mice (ob/ob mice). METHODS: This study used 12-week-old wild-type and ob/ob male mice. The alveolar bone phenotype and periodontal status in the maxilla were analyzed by micro-CT and histological analysis. Osteoclasts in alveolar bone were visualized by TRAP staining. Expressions of inflammatory markers (MMP-9, IL-1ß, and TGF-ß1) and osteoclastogenic markers (RANKL and OPG) in periodontium were analyzed by immunohistochemistry and RT-qPCR. The oral microbiome was analyzed by 16 S rDNA sequencing. RESULTS: CEJ-ABC distance in maxillary molars (M1-M3) of ob/ob mice was significantly higher compared with that of wild-type. The alveolar bone BV/TV ratio was reduced in ob/ob mice compared with wild-type. Higher numbers of osteoclasts were observed in ob/ob mice alveolar bone adjacent to the molar root. Epithelial hyperplasia in gingiva and disordered periodontal ligaments was observed in ob/ob mice. RANKL/OPG expression ratio was increased in ob/ob mice compared with wild-type. Expressions of inflammatory markers MMP-9, IL-1ß, and TGF-ß1 were increased in ob/ob mice compared with wild-type. Oral microbiome analysis showed that beneficial bacteria Akkermansia and Ruminococcaceae_UCG_014 were more abundant in the wild-type mice while the inflammation-related Flavobacterium was more abundant in ob/ob mice. CONCLUSION: In conclusion, ob/ob mice showed higher expressions of inflammatory factors, increased alveolar bone loss, lower abundance of the beneficial bacteria, and higher abundance of inflammatory bacteria in the oral cavity, suggesting leptin-deficient obesity as a risk factor for periodontitis development in ob/ob mice.

Regulatory mechanisms and clinical applications of tumor-driven exosomal circRNAs in cancers.

Malignant tumors seriously affect people's survival and prognosis. Exosomes, as vesicle structures widely existing in human tissues and body fluids, are involved in cell-to-cell transmission. Tumor-derived exosomes were secreted from tumors and involved in the development of carcinogenesis. Circular RNA (circRNA), a novel member of endogenous noncoding RNAs, is widespread in human and play a vital role in many physiological or pathological processes. Tumor-driven exosomal circRNAs are often involved in tumorigenesis and development including the proliferation, invasion, migration and chemo-or-radiotherapy sensitivity of tumor cell by multiple regulatory mechanisms. In this review, we will elaborate the roles and functions of tumor-driven exosomal circRNAs in cancers which may be used as potential cancer biomarkers and novel therapeutic targets.

Survey of Reinforcement-Learning-Based MAC Protocols for Wireless Ad Hoc Networks with a MAC Reference Model.

In this paper, we conduct a survey of the literature about reinforcement learning (RL)-based medium access control (MAC) protocols. As the scale of the wireless ad hoc network (WANET) increases, traditional MAC solutions are becoming obsolete. Dynamic topology, resource allocation, interference management, limited bandwidth and energy constraint are crucial problems needing resolution for designing modern WANET architectures. In order for future MAC protocols to overcome the current limitations in frequently changing WANETs, more intelligence need to be deployed to maintain efficient communications. After introducing some classic RL schemes, we investigate the existing state-of-the-art MAC protocols and related solutions for WANETs according to the MAC reference model and discuss how each proposed protocol works and the challenging issues on the related MAC model components. Finally, this paper discusses future research directions on how RL can be used to enable MAC protocols for high performance.

Adaptive responses of carbon and nitrogen metabolisms to nitrogen-deficiency in Citrus sinensis seedlings.

BACKGROUND: In China, nitrogen (N)-deficiency often occurs in Citrus orchards, which is one of the main causes of yield loss and fruit quality decline. Little information is known about the adaptive responses of Citrus carbon (C) and N metabolisms to N-deficiency. Seedlings of 'Xuegan' (Citrus sinensis (L.) Osbeck) were supplied with nutrient solution at an N concentration of 0 (N-deficiency), 5, 10, 15 or 20 mM for 10 weeks. Thereafter, we examined the effects of N supply on the levels of C and N in roots, stems and leaves, and the levels of organic acids, nonstructural carbohydrates, NH4+-N, NO3--N, total soluble proteins, free amino acids (FAAs) and derivatives (FAADs), and the activities of key enzymes related to N assimilation and organic acid metabolism in roots and leaves. RESULTS: N-deficiency elevated sucrose export from leaves to roots, C and N distributions in roots and C/N ratio in roots, stems and leaves, thus enhancing root dry weight/shoot dry weight ratio and N use efficiency. N-deficient leaves displayed decreased accumulation of starch and total nonstructural carbohydrates (TNC) and increased sucrose/starch ratio as well as a partitioning trend of assimilated C toward to sucrose, but N-deficient roots displayed elevated accumulation of starch and TNC and reduced sucrose/starch ratio as well as a partitioning trend of assimilated C toward to starch. N-deficiency reduced the concentrations of most FAADs and the ratios of total FAADs (TFAADs)/N in leaves and roots. N-deficiency reduced the demand for C skeleton precursors for amino acid biosynthesis, thus lowering TFAADs/C ratio in leaves and roots. N-deficiency increased (decreased) the relative amounts of C-rich (N-rich) FAADs, thus increasing the molar ratio of C/N in TFAADs in leaves and roots. CONCLUSIONS: Our findings corroborated our hypothesis that C and N metabolisms displayed adaptive responses to N-deficiency in C. sinensis seedlings, and that some differences existed between roots and leaves in N-deficiency-induced alterations of and C and N metabolisms.

Overexpression of angiogenic factors and matrix metalloproteinases in the saliva of oral squamous cell carcinoma patients: potential non-invasive diagnostic and therapeutic biomarkers.

BACKGROUNDS: Salivary biomarkers hold huge potential for the non-invasive diagnosis of oral squamous cell carcinoma. Angiogenic factors and matrix-metalloproteinases (MMPs) are highly expressed in OSCC tissue, but their expression patterns in the saliva are unknown. This study aimed to analyze the levels of angiogenic factors and MMPs in tumor tissue and saliva of OSCC patients. METHODS: OSCC-tissue, adjacent normal tissue (ANT), saliva from OSCC patients, and healthy controls were obtained. The expression patterns of angiogenic factors and MMPs were analyzed by immunohistochemistry, protein chip array, and RT-qPCR. RESULTS: Results showed higher expression of ANG, ANG-2, HGF, PIGF, VEGF, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, and TIMP-2 in OSCC-tissues compared to the ANT. Among the overexpressed markers in OSCC-tissues, HGF, VEGF, PIGF, PDGF-BB, MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, and TIMP-2 were significantly upregulated in the saliva of OSCC patients compared to healthy controls. CONCLUSIONS: The levels of HGF, VEGF, PIGF, MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, and TIMP-2 were upregulated both in OSCC tissue and saliva of OSCC patients. Bioinformatic analysis revealed the correlation of these factors with patient survival and cancer functional states in head and neck cancer, indicating these factors as possible saliva-based non-invasive diagnostic/prognostic markers and therapeutic targets of OSCC.

Impact of restrictive red blood cell transfusion strategy on thrombosis-related events: A meta-analysis and systematic review.

BACKGROUND AND OBJECTIVES: There is an ongoing controversy regarding the risks of restrictive and liberal red blood cell (RBC) transfusion strategies. This meta-analysis assessed whether transfusion at a lower threshold was superior to transfusion at a higher threshold, with regard to thrombosis-related events, that is, whether these outcomes can benefit from a restrictive transfusion strategy is debated. MATERIALS AND METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials and Scopus from inception up to 31 July 2021. We included randomized controlled trials (RCTs) in any clinical setting that evaluated the effects of restrictive versus liberal RBC transfusion in adults. We used random-effects models to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) based on pooled data. RESULTS: Thirty RCTs involving 17,334 participants were included. The pooled RR for thromboembolic events was 0.65 (95% CI 0.44-0.94; p = 0.020; I2  = 0.0%, very low-quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR = 0.83; 95% CI 0.64-1.09; p = 0.180; I2  = 0.0%, very low-quality evidence) or myocardial infarction (RR = 1.05; 95% CI 0.87-1.26; p = 0.620; I2  = 0.0%, low-quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced (1) thromboembolic events in RCTs conducted in North America and (2) myocardial infarctions in the subgroup of RCTs where the restrictive transfusion threshold was 7 g/dl but not in the 8 g/dl subgroup (with a liberal transfusion threshold of 10 g/dl in both subgroups). CONCLUSIONS: A restrictive (relative to liberal) transfusion strategy may be effective in reducing venous thrombosis but not arterial thrombosis.

Boron-mediated amelioration of copper-toxicity in sweet orange [Citrus sinensis (L.) Osbeck cv. Xuegan] seedlings involved reduced damage to roots and improved nutrition and water status.

'Xuegan' (Citrus sinensis) seedlings were fertilized 6 times weekly for 24 weeks with 0.5 or 350 µM CuCl2 and 2.5, 10 or 25 µM H3BO3. Cu-toxicity increased Cu uptake per plant (UPP) and Cu concentrations in leaves, stems and roots, decreased water uptake and phosphorus, nitrogen, calcium, magnesium, potassium, sulfur, boron and iron UPP, and increased the ratios of magnesium, potassium, calcium and sulfur UPP to phosphorus UPP and the ratios of leaf magnesium, potassium and calcium concentrations to leaf phosphorus concentration. Many decaying and dead fibrous roots occurred in Cu-toxic seedlings. Cu-toxicity-induced alterations of these parameters and root damage decreased with the increase of boron supply. These results demonstrated that B supplementation lowered Cu uptake and its concentrations in leaves, stems and roots and subsequently alleviated Cu-toxicity-induced damage to root growth and function, thus improving plant nutrient (decreased Cu uptake and efficient maintenance of the other nutrient homeostasis and balance) and water status. Further analysis indicated that the improved nutrition and water status contributed to the boron-mediated amelioration of Cu-toxicity-induced inhibition of seedlings, decline of leaf pigments, large reduction of leaf CO2 assimilation and impairment of leaf photosynthetic electron transport chain revealed by greatly altered chlorophyll a fluorescence (OJIP) transients, reduced maximum quantum yield of primary photochemistry (Fv/Fm), quantum yield for electron transport (ETo/ABS) and total performance index (PIabs,total), and elevated dissipated energy per reaction center (DIo/RC). To conclude, our findings corroborate the hypothesis that B-mediated amelioration of Cu-toxicity involved reduced damage to roots and improved nutrient and water status. Principal component analysis showed that Cu-toxicity-induced changes of above physiological parameters generally decreased with the increase of B supply and that B supply-induced alterations of above physiological parameters was greater in 350 µM Cu-treated than in 0.5 µM Cu-treated seedlings. B and Cu had a significant interactive influence on C. sinensis seedlings.

Molecular and Physiological Responses of Citrus sinensis Leaves to Long-Term Low pH Revealed by RNA-Seq Integrated with Targeted Metabolomics.

Low pH-induced alterations in gene expression profiles and organic acids (OA) and free amino acid (FAA) abundances were investigated in sweet orange [Citrus sinensis (L.) Osbeck cv. Xuegan] leaves. We identified 503 downregulated and 349 upregulated genes in low pH-treated leaves. Further analysis indicated that low pH impaired light reaction and carbon fixation in photosynthetic organisms, thereby lowering photosynthesis in leaves. Low pH reduced carbon and carbohydrate metabolisms, OA biosynthesis and ATP production in leaves. Low pH downregulated the biosynthesis of nitrogen compounds, proteins, and FAAs in leaves, which might be conducive to maintaining energy homeostasis during ATP deprivation. Low pH-treated leaves displayed some adaptive responses to phosphate starvation, including phosphate recycling, lipid remodeling, and phosphate transport, thus enhancing leaf acid-tolerance. Low pH upregulated the expression of some reactive oxygen species (ROS) and aldehyde detoxifying enzyme (peroxidase and superoxidase) genes and the concentrations of some antioxidants (L-tryptophan, L-proline, nicotinic acid, pantothenic acid, and pyroglutamic acid), but it impaired the pentose phosphate pathway and VE and secondary metabolite biosynthesis and downregulated the expression of some ROS and aldehyde detoxifying enzyme (ascorbate peroxidase, aldo-keto reductase, and 2-alkenal reductase) genes and the concentrations of some antioxidants (pyridoxine and γ-aminobutyric acid), thus disturbing the balance between production and detoxification of ROS and aldehydes and causing oxidative damage to leaves.

Notoginsenoside R1 Promotes Migration, Adhesin, Spreading, and Osteogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stromal Cells.

Cellular activities, such as attachment, spreading, proliferation, migration, and differentiation are indispensable for the success of bone tissue engineering. Mesenchymal stromal cells (MSCs) are the key precursor cells to regenerate bone. Bioactive compounds from natural products had shown bone regenerative potential. Notoginsenoside R1 (NGR1) is a primary bioactive natural compound that regulates various biological activities, including cardiovascular protection, neuro-protection, and anti-cancer effects. However, the effect of NGR1 on migration, adhesion, spreading, and osteogenic differentiation of MSCs required for bone tissue engineering application has not been tested properly. In this study, we aimed to analyze the effect of NGR1 on the cellular activities of MSCs. Since human adipose-derived stromal cells (hASCs) are commonly used MSCs for bone tissue engineering, we used hASCs as a model of MSCs. The optimal concentration of 0.05 µg/mL NGR1 was biocompatible and promoted migration and osteogenic differentiation of hASCs. Pro-angiogenic factor VEGF expression was upregulated in NGR1-treated hASCs. NGR1 enhanced the adhesion and spreading of hASCs on the bio-inert glass surface. NGR1 robustly promoted hASCs adhesion and survival in 3D-printed TCP scaffold both in vitro and in vivo. NGR1 mitigated LPS-induced expression of inflammatory markers IL-1ß, IL-6, and TNF-α in hASCs as well as inhibited the RANKL/OPG expression ratio. In conclusion, the biocompatible NGR1 promoted the migration, adhesion, spreading, osteogenic differentiation, and anti-inflammatory properties of hASCs.

The protocol of a prospective, multicenter, randomized, controlled phase III study evaluating different cycles of oxaliplatin combined with S-1 (SOX) as neoadjuvant chemotherapy for patients with locally advanced gastric cancer: RESONANCE-II trial.

BACKGROUND: Curing locally advanced gastric cancer through surgery alone is difficult. Adjuvant and neoadjuvant chemotherapy bring potential benefits to more patients with gastric cancer based on several clinical trials. According to phase II studies and guidelines, SOX regimen as neoadjuvant chemotherapy is efficient. However, the optimal duration of neoadjuvant chemotherapy has not been established. In this study, we will evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer. METHODS: RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Eligible patients will be registered, pre-enrolled and receive three cycles of SOX, after which tumor response evaluations will be carried out. Those who show stable disease or progressive disease will be excluded. Patients showing complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery; or group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival, and safety. DISCUSSION: This study is the first phase III randomized trial to compare the cycles of neoadjuvant chemotherapy using SOX for resectable locally advanced cancer. Based on a total of six to eight cycles of perioperative chemotherapy usually applied in locally advanced gastric cancer, patients in group A can be considered to have completed all perioperative chemotherapy, the results of which may suggest the feasibility of using chemotherapy only before surgery in gastric cancer. TRIAL REGISTRATION: Registered prospectively in the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) with registration number ChiCTR1900023293 on May 21st, 2019.

LncRNA PCGEM1 enhances metastasis and gastric cancer invasion through targeting of miR-129-5p to regulate P4HA2 expression.

AIM: Aberrantly expressed long non-coding RNAs (lncRNAs) are critical instigators of gastric cancer (GC) progression and metastasis. The ceRNA (competing endogenous RNAs) network is well-known in modulating tumor pathological and physiological processes. This research aims to determine the more effective molecular mechanisms of lncRNA PCGEM1 (prostate cancer gene expression marker 1). METHODS: Bioinformatics database and Ago2-RIP were performed to predict and verify the potential targets of lncRNA PCGEM1. Both gain- and loss-of-function experiments were carried out to dissect the biological functions of RNAs. Fluorescence in situ hybridization, dual-luciferase reporter assays, western blot, and real-time PCR (RT-PCR) experiments were utilized to determine the pathophysiological pathways of competitive endogenous RNAs (ceRNAs). RESULTS: GC cells expressed high levels of cytoplasmic PCGEM1. Loss-of-function experiments displayed that the silencing of PCGEM1 suppressed metastatic and invasive cell qualities. PCGEM1 was also found to have associations with miR-129-5p. Subsequently, luciferase reporter and RIP experiments, together with RT-PCR, verified that PCGEM1 functioned as a ceRNA of P4HA2 (Prolyl 4-Hydroxylase Subunit Alpha 2) via sponging miR-129-5p to up-regulate P4HA2 expression. Finally, the rescue assays determined that P4HA2 overexpression rescued the inhibited cell invasion and metastasis caused by PCGEM1 down-regulation. CONCLUSION: These findings found that an over-expression of PCGEM1 in GC acts as a miR-129-5p sponge, leading to higher levels of P4HA2. The PCGEM1/miR-129-5p/P4HA2 axis was confirmed to possess a crucial role in GC metastasis and invasion, suggesting its utility as a potential diagnostic and therapeutic biomarker.

A SEER population analysis of stage IB resected gastric cancer: who can benefit from adjuvant therapy?

Objective: The benefit of adjuvant therapy (AT) remains controversial in stage IB gastric cancer (GC). This study aimed to offer a reference for the rational indications of AT.Methods: We retrospectively included 1216 stage IB GC who experienced curative surgery from the SEER database between 2004 and 2015. These patients were allocated into two groups: Group AT and Group surgery alone (Group SA). We established a nomogram to predict OS and then divided whole cohort into low-risk and high-risk groups based on the OS predicted by the nomogram.Results: Six variables, which were significantly related with OS of entire patients after matched, were incorporated in the nomogram. These variables were age, examined lymph nodes, tumor site, marital, family income and stage IB. The C-index of the model was 0.637 and the calibration curve showed that the anticipated values were in accordance with the actual values. The decision curve demonstrated that the optimal clinical impact was achieved when the threshold possibility was 0-56%. Then, the entire cohort was separated into low-risk (≤159 points) as well as high-risk (>159 points) groups based on the projected 5-year OS of recursive partitioning analysis. Group SA revealed a significantly poorer OS than Group AT for high-risk patients (p < .001); on the other hand, there was a comparable OS for low-risk patients (p = .361).Conclusions: We have developed an effective, intuitional and applied prognostic tool to clinical decision-making. For stage IB GC after surgical resection, AT was only recommended for high-risk patients. However, AT may be dispensable for low-risk patients.

Patient-generated subjective global assessment versus nutritional risk screening 2002 for gastric cancer in Chinese patients.

Aim: Patient-Generated Subjective Global Assessment (PG-SGA) and Nutritional Risk Screening 2002 (NRS2002) are used to evaluate patients' nutritional status. Materials & methods: The data of 114 gastric cancer patients with pyloric obstruction treated between July 2016 and July 2017 were assessed retrospectively. Results: Based on clinical evaluation, 70.1% had malnutrition, with 61.4% at nutritional risk by NRS2002 and 66.7% by PG-SGA. The area under the receiver operating characteristic curve was 0.858 for PG-SGA and 0.706 for NRS2002. Sensitivity and specificity were 89 and 85% for PG-SGA and 78 and 76% for NRS2002. In both assessments, patients at risk showed more postoperative complications. Conclusion: PG-SGA was more suitable for evaluating the preoperative nutritional status of gastric cancer patients with pyloric obstruction, with higher diagnostic efficacy.

LINC00163 inhibits the invasion and metastasis of gastric cancer cells as a ceRNA by sponging miR-183 to regulate the expression of AKAP12.

BACKGROUND: Gastric cancer (GC) is the most common and aggressive cancer of the digestive system and poses a serious threat to human health. Since genes do not work alone, our aim was to elucidate the potential network of mRNAs and noncoding RNAs (ncRNAs) in this study. METHODS: Transcriptome data of GC were obtained from TCGA. R and Perl were used to obtain the differentially expressed RNAs and construct a competing endogenous RNA (ceRNA) regulatory network. To investigate the biological functions of differentially expressed RNAs, loss-of-function and gain-of-function experiments were performed. Real-time PCR (RT-qPCR), western blot analysis, dual-luciferase reporter assays and fluorescence in situ hybridization were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs). RESULTS: Based on TCGA data and bioinformatics analysis, we identified the LINC00163/miR-183/A-Kinase Anchoring Protein 12 (AKAP12) axis. We observed that AKAP12 was weakly expressed in GC and suppressed invasion and metastasis in GC cells, which could be abolished by miR-183. In addition, LINC00163 can be used as a ceRNA to inhibit the expression of miR-183, thus enhancing the anticancer effect of AKAP12. CONCLUSION: Our results demonstrated that weak LINC00163 expression in GC can sponge miR-183 to promote AKAP12. We established that the LINC00163/miR-183/AKAP12 axis plays an important role in GC invasion and metastasis and may be a potential biomarker and target for GC treatment.

Validation of prognostic accuracy of the SOFA score, SIRS criteria, and qSOFA score for in-hospital mortality among cardiac-, thoracic-, and vascular-surgery patients admitted to a cardiothoracic intensive care unit.

SEPSIS-3 DEFINITION: Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. The clinical criteria of sepsis include organ dysfunction, which is defined as an increase of two points or more on the sequential organ failure assessment (SOFA). For patients with infection, an increase of 2 SOFA points yields an overall mortality rate of 10%. Patients with suspected infection who are likely to have a prolonged intensive care unit (ICU) stay or to have in-hospital mortality can be promptly identified at the bedside with a quick SOFA (qSOFA) score of 2 or higher. IMPORTANCE: The sepsis-3 criteria have emphasized the value of a change of two or more points on the SOFA, introduced the qSOFA, and removed the systemic inflammatory response syndrome (SIRS) criteria from the sepsis definition. OBJECTIVE: To externally validate and assess the discriminatory capacities of an increase in the SOFA score by two or more points, the presence of two or more SIRS criteria, or a qSOFA score of 2 or more points for outcomes in 5109 patients, the vast majority of whom were postcardiac surgery patients who were admitted to a Cardiothoracic Surgical ICU in Singapore. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort analysis of 5109 patients with an infection-related primary admission diagnosis in the cardiothoracic intensive care unit (CTICU) at the National University Hospital (NUH) in Singapore from 2010 to 2016. EXPOSURES: The SOFA, qSOFA, and SIRS criteria were applied to the data representing the worst condition within 24 hours of ICU admission. MAIN OUTCOMES AND MEASURES: The primary outcome was in-hospital mortality. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: In 5109 patients, the average mortality of patients with an increase in the SOFA scores of less than 2 points was 3.5% (n = 64), and it was 6% (n = 199) for those with an increase in the SOFA scores of 2 or more points. The mortality of patients with an increase in the qSOFA scores of less than 2 points was 2.6% (n = 7), and it was 5.3% (n = 256) for those with an increase in the qSOFA scores of 2 or more points. The mortality of patients with an increase in the SIRS criteria of less than 2 points was 3.6% (n = 30), and it was 5.4% (n = 233) for those with an increase in the SIRS criteria of 2 or more points. The AUROC of in-hospital mortality of patients with an increase in the SOFA, qSOFA, and SIRS criteria of 2 or more points was 0.96, 0.95, and 0.95, respectively. CONCLUSIONS AND RELEVANCE: In adults with suspected infection admitted to the CTICU in NUH, the change in in-hospital mortality between patients with an increase in SOFA scores of less than 2 and those with an increase of 2 or more was 2.5 percentage points. In contrast to other studies, the absolute change in mortality was nearly the same compared to the qSOFA and SIRS criteria, and the qSOFA score had the greatest percentage increase of 104%, compared to 71% for the SOFA score and 50% for the SIRS criteria. Besides, from the perspective of discriminatory capacities, an increase in SOFA scores of 2 or more did not demonstrate significantly greater prognostic accuracy for in-hospital mortality than equivalent increases in qSOFA scores or SIRS criteria. These findings suggest distinctive characteristics of the study population in the CTICU that are different from the general population.

Lowe syndrome with extremely short stature: growth hormone deficiency may be the pathogeny.

Lowe syndrome is an x-linked disorder characterized by congenital cataracts, nervous system abnormalities and renal tubular dysfunction. With the rising number of reported cases, more patients are found to suffer from endocrine abnormalities. Hereby, three Chinese patients with typical symptoms and extremely short stature were described. The OCRL gene was analyzed. A combination of blood biochemistry and radiological examinations were performed. Growth hormone provocation test was taken in one patient. Nucleotide sequence analysis revealed a de novo novel hemizygous mutation (c.2290_2291delinsCT) in exon 21 in an adolescent boy. As indicated by the growth hormone provocation test, the boy had growth hormone deficiency. The other two patients were brothers with extremely short stature, and manifested the same hemizygous mutation (c.2581G > A) in exon 23. It was speculated that the mutation of OCRL gene could lead to deficiency of growth hormone, for which an early growth hormone intervention may be beneficial.